Cuprous Oxide-Based Dual Catalytic Nanostructures for Tumor Vascular Normalization-Enhanced Chemodynamic Therapy

Abstract

The abnormal blood vessels in tumor sites, causing poor tumor perfusion and hypoxia environment, restrict the chemodynamic therapy (CDT) potency significantly. To attain the synergistic therapy of tumor vascular normalization with CDT, herein, we constructed a dual-functional nanocatalyst with a simple structure, cuprous oxide by dextran (Cu 2 O@Dex), to restore proper tumor perfusion and tumor oxygenation. The in vitro experiment outcomes illustrated that Cu 2 O@Dex hardly releases Cu (Cu +/2+ ) under neutral conditions, which avoids unnecessary catalytic reaction in blood circulation. Under the weak acidic condition (pH 6.5), Cu 2 O@Dex begins to release Cu (Cu +/2+ ), catalyzing the nitric oxide (NO) generation for vascular normalization. Also, Cu 2 O@Dex further releases a large amount of Cu (Cu +/2+ ) under more acidic intratumor cells (pH 5.5), fast catalyzing the hydroxyl radical (•OH) generation for CDT. The in vivo experiment observations verified that Cu 2 O@Dex could improve tumor perfusion significantly 3 h post injection, which lasted for more than 144 h. The effective perfusion (Hoechst 33342 + ) area in the Cu 2 O@Dex group was 3.8-fold higher than that in the phosphate buffer saline (PBS) group after 48 h of injection, confirming the effectiveness of Cu 2 O@Dex to induce vascular normalization. Noticeably, tumor vascular normalization further enhanced the therapeutic effect of CDT through delivery of H 2 O 2 generator juglone (JUG) more smoothly. The antitumor efficacy of Cu 2 O@Dex plus JUG was 86.5% with no obvious toxicity. Overall, our design achieved the dual-catalytic effects integrated in one simple nanostructure for tumor vascular normalization-enhanced CDT.

A hypochlorite-activatable persistent luminescence nanoprobe for assisted tumor resection

“…4(b)). 33 The LPS group showed a 1.9-fold increase compared to the control group (** p < 0.01) and a 2.3-fold increase compared to the LPS-taurine group (*** p < 0.001). These results demonstrated the impressive potential of ZGC@P&A for the specific detection of ClO − in vivo .…”

Transition-Metal-Oxide-Based Nanozymes for Antitumor Applications

“…Cuprous oxide (Cu 2 O), as a stable copper-based nanomedicine, has been confirmed to promote tumor cell apoptosis by producing ROS in melanoma, bladder cancer, and cervical cancer cell lines [ 82 , 83 ]. Wang et al [ 84 ]. constructed a bifunctional nanocatalyst called Cu 2 O@Dex, which was composed of dextran.…”

The potential of vascular normalization for sensitization to radiotherapy

“…For example, acid-responsive mesoporous silica nanoparticles (MSN) intelligently release dopamine, which can significantly inhibit vascular endothelial cell migration and tubule formation, and promote tumor vascular normalization [ 97 ]. As well as dextran combined with cuprous oxide (Cu 2 O@Dex), which releases Cu (Cu +/2+ ) under acidic conditions, catalyzes the production of NO for vascular normalization [ 98 ]. Du et al used 8-hydroxyquinoline (HQ)-modified AuNPs to obtain AuHQ, which reduces a variety of angiogenic growth factors by inhibiting oxidative stress in tumors and reducing expression by inhibiting oxidative stress in tumors.…”